This report covers three projects. The major project is a study of the biosynthesis, mode of action, and metabolism of Gamma-hydroxybutyrate (GHB). Biological factors which regulate the enzyme that converts GHB to succinic semialdehyde (SSA) have been studied. Both in vivo and in vitro studies on the conversion of putrescine, a know precursor of GABA, to GHB are underway. The conversion of arginine and Beta-hydroxybutyrate to GHB are also being studied. A study concerning the effect of elevated levels of the ketone body, acetoacetate, on the formation of GTP and cGMP in the brain has been completed. A third study concerned the in vivo incorporation of 2-deoxyglucose into glycogen. This study has also been completed. The results indicate that 2-deoxyglucose is incorporated, but only to a very small extent. The goals of this project are 1) to elucidate the role of naturally occurring GHB in the brain and in peripheral tissues; 2) to understand the biochemical basis for the profound pharmacological actions of GHB; and 3) to investigate the pathways of biosynthesis and degradation as well as the normal metabolic factors and pharmacological agents which control these pathways.